Page 223 - Biomedical Engineering and Design Handbook Volume 2, Applications

202 MEDICAL DEVICE DESIGN

7.6.5 Determining Package Integrity
The FDA has recognized ISO 11607 as a consensus standard, which states that, “The manufacturer
shall demonstrate the integrity of the package by testing the package. This can be accomplished by
physical tests.” Examples of physical tests as described in the ISO 11607 standard include internal
pressure test, and dye penetration test, gas sensing test, and vacuum leak test. All of these methods
have their advantages and disadvantages.
Microbial Challenge/Product Sterility Test Methods. There are really two types of microbial bar-
rier tests: those performed on materials and those performed on whole packages. Microbial barrier
tests on materials are performed by packaging manufacturers to ensure that their materials are imper-
vious to microorganisms while allowing sterilant gases to permeate for product sterilization pur-
poses. This is why “breathable” materials are used for sterile barrier systems. These tests are
typically performed using ASTM F1608, “Microbial Ranking of Porous Packaging Materials
(Exposure Chamber Method).” Microbial barrier testing of materials is significantly less controver-
sial than microbial testing of whole packages since this methodology lends itself to some level of
standardization and control. Determining the microbial barrier characteristics of materials is very
different from the methods required for a whole package testing. A whole package test is signifi-
cantly more complex than a single material, and whole package microbial challenge testing has long
been discredited as a reliable means of determining package (sterile barrier system) integrity. For this
reason the remainder of the package integrity discussion focuses on physical test methods for deter-
mining package integrity.
Physical Test Methods. Some of the physical test methods have been available for many years as
published ASTM standards. Recently, the industry has taken a closer look at the validity and effec-
tiveness of these methods and has developed new methods for evaluating package integrity.
Visual Inspection. ASTM Subcommittee F2 published standard F1886-98, “Standard Test
Method for Determining Integrity of Seals for Medical Packaging by Visual Inspection, to help detail
a methodology for visual inspection. This standard describes a method to visually detect channel
defects in package seals down to a width of 0.003 in (75 μm) with a 60 to100 percent probability,
depending on the package type and size of channel. It provides attribute data (accept/reject) for pack-
age integrity of finished, unopened packages. It is generally not effective in detecting pinholes and
minute tears in package substrates. In addition, visual inspection cannot be used for packages with
two opaque substrates, as transparency of the seal surfaces is essential to the inspection. Its most
applicable attribute is for monitoring package quality in production to detect any significant changes
in heat-sealing process parameters, which may provide the first indication that the process is out of
control. Additional testing using more sensitive methods for leak detection of packages suspicious
of having defects may be warranted to confirm whether the channel or void is in fact an unsealed
area. Visual inspection is not considered to be the only means by which the manufacturer should
evaluate for package integrity.
Internal Pressure Test. The internal pressure or bubble leak test applies an internal pressure to
the sterile package while it is submerged in water and notes any escaping air bubbles. The Flexible
Packaging Association’s (FPA) committee, Sterilization Packaging Manufacturers Council (SPMC),
originally published this standard for testing packaging integrity. The standard was entitled
FPA/SPMC Standard 005-96, “Standard Test Method for Detection of Leaks in Heat Seal Packages-
Internal Pressurization Method,” and has since been adopted by ASTM and published as F2096-04,
“Standard Test Method for Detecting Gross Leaks in Medical Packaging by Internal Pressurization
(Bubble Test).” This has become the industry’s definitive method in package validation studies for
determining the integrity of the sterile barrier system.
As the standard describes in the “Significance and Use” section:
The internal pressurization test method provides a practical way to examine packages for gross leaks,
which may render the product nonsterile.
This test method is extremely useful in a test laboratory environment where no common package
material/size exists.